This proposal will assess the clinical relevance of assays for 16alphaOHE1, and other estrogen metabolites in predicting the degree and rate of bone loss in women at risk for osteoporosis. The offerors propose to determine the levels of estrogen metabolites in saliva, urine, and blood of women at risk for osteoporosis. The overall plan is to use a cross-sectional study of women 40 to 70 years of age, and a longitudinal study of women 50 to 57 years of age. Levels of 2-hydroxyestrone (2OHE1) or 2-methoxyestrone, 16-alpha-hydroxyestrone (16alphaOHE1), estriol (E3), and estradiol (E2) will be correlated with bone density measurements. The preliminary and background data suggest that 2OHE1 and/or E3 are the best independent biomarker for detection of decreased vertebral bone density (VBD). The hypothesis proposed is that estrogen metabolism plays a critical role in disease susceptibility and disease severity, specifically, faster bone loss will be distinguished by increased 16alphaOHE1. The investigation is based on the theory that there are two major types of osteoporosis, fast loss of bone mineral density at early postmenopause (Type I) and slow cumulative loss of density in old age (Type II). The goal of the study is to determine if the quantitation of 16alphaOHE1 will lead to the identification of the Type I osteoporosis and allow for intervention therapy. Univariate and multivariate analyses of each hormone level in each tissue will be correlated with body-mass index, smoking status, estrogen use, waist-hip ratio, bone mass, rate of bone loss, race and age. These data will be used for the development of estrogen metabolite assay kits that predicts osteoporosis. Also, there is a possibility that in the future, the kits will be applied to the testing for other estrogen-dependent diseases.